Botanical supplements with estrogenic activity including soy, wild yam, licorice root and dong quai are widely consumed by women seeking to gain relief from menopausal symptoms or to slow bone loss and/or cognitive decline during aging. However, very little is known about the efficacy or safety of most of these compounds. The proposed Botanical Research Center will address this important unmet public health need through a highly integrated set of Research Projects and Cores. Verified botanical materials will be provided to all ofthe Projects by Core A as raw materials, extracts and pure compound isolates. Project 3 will use a rodent model to examine the impact of these botanical estrogens on cognifive funcfion and bone health. Insights about mechanism of action gained from in vitro and cell-based studies in Project 1 and informafion on pharmacokinetics and bioavailability available from Core B will be used to select materials and doses for these studies. We will use a well-characterized battery of cognifive tasks that tap multiple cognifive domains and mulfiple memory systems, and that are sensitive to both the beneficial and detrimental effects of estrogens. We will include as positive controls estrogens with known activities, and, in collaboration with Project 2, we will evaluate brain and bone health in the same experimental animals allowing direct comparisons of the relative efficacy and safety of botanical estrogens in these two important target fissues. Compounds that are identified as active in brain and/or bone will be studied further to identify whether they demonstrate an ER-mediated mechanism of acfion, and, if so, the involvementof well-established ER signaling pathways. Because many botanical estrogens show selecfivity for ERp, we hypothesize that they will act through ERp-mediated pathways to alter both cognifive function and bone health. In summary our research will fill a critical gap in knowledge by providing high quality preclinical data addressing the efficacy, safety and mechanism of action of botanical estrogens derived from soy, wild yam, licorice root and dong quai on two very important estrogen responsive endpoints: cognitive funcfion and bone. These studies will provide crifical data needed for the appropriate design of clinical trials in the future.